The
endocannabinoid system is involved in a host of homeostatic and physiologic functions, including modulation of
pain and
inflammation. The specific roles of currently identified
endocannabinoids that act as
ligands at endogenous
cannabinoid receptors within the central nervous system (primarily but not exclusively CB 1 receptors) and in the periphery (primarily but not exclusively CB 2 receptors) are only partially elucidated, but they do exert an influence on nociception. Exogenous plant-based
cannabinoids (phytocannabinoids) and chemically related compounds, like the
terpenes, commonly found in many foods, have been found to exert significant
analgesic effects in various
chronic pain conditions. Currently, the use of Δ9-tetrahydrocannabinol is limited by its psychoactive effects and predominant delivery route (smoking), as well as regulatory or legal constraints. However, other phytocannabinoids in combination, especially
cannabidiol and β-
caryophyllene, delivered by the oral route appear to be promising candidates for the treatment of
chronic pain due to their high safety and low adverse effects profiles. This review will provide the reader with the foundational basic and clinical science linking the
endocannabinoid system and the phytocannabinoids with their potentially therapeutic role in the management of chronic
pain.